NASA interest fuels bone-loss research

Tests are being conducted in space, but they'll have widespread application on earth.

By Susan J. Landers, amednews staff. Jan. 7, 2002.

Washington -- What do astronauts, people with spinal cord injuries and millions of older women have in common? All face a heightened risk of fractures resulting from loss of bone mass.

The effects of prolonged weightlessness have led many astronauts to lose significant amounts of bone mass. And, once lost, the bone is difficult to gain back.

Likewise, muscle atrophy and bone loss are major complications of spinal cord injury.

And osteoporosis affects a large number of postmenopausal women, a burgeoning group as the baby boom generation moves beyond age 50.

Some believe solutions to the common problem are the same for all three groups and, to prove the point, are conducting a variety of studies.

Paul Kostenuik, PhD, a research scientist with Amgen Inc., the large biotechnology firm, is focusing on osteoprotegerin, or OPG, a protein manufactured by the body to prevent bone loss.

Astronauts have lost as much as 13% of their bone mass after spending only months aboard a space station.

"We've spent the last few years trying to turn this natural protein into a safe, effective and convenient therapeutic for bone loss that could be used for osteoporosis, cancer or rheumatoid arthritis or any number of things that cause bone loss," he said.

Dr. Kostenuik, working with a commercial firm that helps smooth the way for National Aeronautics and Space Administration flight experiments, gained permission to test OPG aboard the space shuttle Endeavour last month.

Mice injected with either OPG or a placebo accompanied the astronauts on the 12-day mission to bring home three of the men who have lived on the international space station since last summer.

Dr. Kostenuik, still awaiting the return of the mice at press time, wasn't sure a 12-day mission would be long enough to test the effectiveness of OPG in the mice. "That's the $64,000 question," he said. "We are going to be very anxious to see if it is enough time. We do know that bone loss occurs very rapidly in space."

But NASA's interest extends way beyond missions of such short duration. The space agency is thinking about bigger things, including human exploration of Mars. Such a lengthy flight is likely to result in extreme bone loss unless an effective treatment is found. Astronauts who have spent only months aboard the space station Mir, for example, have lost as much as 13% of their bone mass.

NASA awarded a contract to the National Space Biomedical Research Institute in 1997 to work to prevent or solve such health problems related to long-duration space travel.

NSBRI is a consortium of 12 institutions, including Baylor College of Medicine, Harvard Medical School, Johns Hopkins University, and Massachusetts Institute of Technology.

Meanwhile, Jay Shapiro, MD, who heads a bone loss study team funded by NASA, is studying zoledronate, a newly approved and powerful bisphosphonate, which, like OPG, slows the rate of bone absorption.

"Throughout our lives, new bone is formed and old bone is absorbed," said Dr. Shapiro, who is also a professor of medicine at the Uniformed Services University of the Health Sciences. "Bisphosphonates inhibit the cycle of bone breakdown that occurs, keeping you from losing as much and allowing the bone-forming processes a little more breathing room," he said.

Dr. Shapiro is currently using the drug on spinal cord injury patients to determine its effectiveness.

The risk of fracture is great for adults and children immobilized by spinal cord or brain injuries, strokes, neuromuscular disorders or developmental disorders such as spina bifida or cerebral palsy, he noted. "And once you lose muscle function, you will lose bone," he said. This is also true in space for astronauts because their muscles no longer have to function against gravity, he added.

Space travel effects

Bone loss among astronauts is greatest in the legs. In flight, astronauts exert enough muscle tension in their upper trunks and arms that they don't lose bone there, Dr. Shapiro explained. Space flight also causes shifts in fluid and blood flow that favor retaining bone in the upper trunk while losing it in the lower trunk, he added.

As head of the consortium's Bone Loss Research Team, Dr. Shapiro is scheduled to meet this month with NASA officials to discuss testing zoledronate aboard a future shuttle mission. But instead of injecting mice with the drug, Dr. Shapiro would like to inject the astronauts.

He believes zoledronate, like its related bisphosphonates, could be very helpful in stanching astronauts' bone loss. While the drugs appear to be safe and effective, "You never know how good they are until you fly them," he noted.

But bisphosphonates do have a proven safety record, Dr. Shapiro said.

"We've got a zillion people around the world taking bisphosphonates," he noted. The drugs are even administered to infants at the Osteogenesis Imperfecta Clinic, which Dr. Shapiro directs at the Kennedy Krieger Institute in Baltimore.

Many women already take the bisphosphonate alendronate, marketed under the name Fosamax, by Merck, to prevent bone loss. But alendronate is not a good candidate for space travel, or for use with infants, as it can cause severe digestive upsets in some people, and users of the drug are cautioned to take the medication on an empty stomach and not lie down for a half-hour.

In Dr. Shapiro's one-year study on spinal cord injury patients, some patients will receive zoledronate intravenously at widely spaced intervals while others will receive a placebo.

Measurements will be taken throughout the study of patients' bone density and muscle structure.

"If we can show that the medication inhibits bone loss in spinal cord injury patients, then it is likely that it would be effective in space," Dr. Shapiro said.

Zoledronate is administered intravenously and might well be effective for a year, Dr. Shapiro said, another boon for space travel of long duration.

The zoledronate study isn't the only bone loss project under way at NSBRI. Barely perceptible vibrations also may stimulate bone growth, say researchers at the State University of New York at Stony Brook.

They discovered that normally active animals exposed to 10 minutes per day of low-magnitude, high-frequency vibrations experienced increased bone formation when compared to a control group.

In addition, when animals prevented from regular weight-bearing activity were exposed to 10 minutes of vibrations per day, bone formation remained at near-normal levels.

After all is said and done, a combination of treatments might serve the astronauts well, Dr. Shapiro said. "The best guess is that there would be some type of resistance exercise to retain muscle and, indirectly, bone, and some pharmacologic agent to decrease the rate of active bone absorption," he said.

Note: Reporter Susan Landers' husband is among the spinal cord injury patients involved in Dr. Shapiro's zoledronate study.